The biogenic amines have been broadly implicated in neurological disease and affective disorders. The ingestion of ethyl alcohol has been shown to significantly perturb the metabolism, the turnover rates, the subcellular distribution, and the endogenous levels of the biogenic amines. Such neurochemical alterations may, therefore, be of significance in the development of either physical or psychological dependence. Preliminary results indicate that significant alterations in the whole brain levels and turnover rates of the catecholamines occur when ethyl alcohol is continuously adminstered to mice by inhalation for 72 hr. Following withdrawal, further significant changes in these parameters and a withdrawal reaction occur. It is proposed to continue these studies by determining the whole brain catecholamine levels and turnover rates at intervals following withdrawal until they reach either control levels or new steady state levels. The study will be expanded to include the determination of changes in subcellular distribution of the biogenic amines during intoxication and following withdrawal. Similar experiments will be carried out employing the adminstration of alcohol in a liquid diet. The time course of the various changes in the biogenic amines will be correlated to the time course of the development of physical dependence and the withdrawal reaction.